According to a recent study, the rate of genetic changes in the monkeypox virus was higher than expected.
GS paper: 3 Science and Technology- developments and their applications and effects in everyday life.
What exactly is genome sequencing, and what are the advantages? Also, list the steps that India has taken in this direction. (250 words)
- Until recently, monkeypox virus infections were largely limited to countries in Central and Eastern Africa, where it was first reported in humans in 1970.
- Several cases were identified in Spain early in 2022, and several cases were reported from countries where the disease is not endemic, including regions in Europe and North America, and in patients with no history of travel to endemic regions.
- The World Health Organization (WHO) declared the 2022 monkeypox outbreak a Public Health Emergency of International Concern after a rapid increase in cases (PHEIC).
- Over 25,000 cases of monkeypox had been reported as of early August 2022 from 83 countries, 76 of which had never previously reported monkeypox.
Genome sequences to look forward
- The increased use of genomics as a tool for understanding outbreaks in the last half-decade has left an indelible mark during the ongoing COVID-19 pandemic and has resulted in a wider deployment of sequencing infrastructure around the world.
- Pathogen genomic surveillance could provide unique insights into the outbreak, track pathogen spread, and provide enormous opportunities for public health decision-making as well as epidemiology.
- To date, researchers from around the world have made over 650 complete genome sequences of monkeypox isolates available in public domain databases such as GISAID and GenBank.
- This includes over 600 genomes sequenced this year alone from over 35 countries, including the genomes of two isolates from Kerala, India.
Evolution has been accelerated.
- The DNA genome of the monkeypox virus is approximately 2,00,000 base pairs in size, roughly six times that of SARS-CoV-2. The monkeypox virus, like other viruses, evolves through the accumulation of genetic errors, or mutations, in its genome as it replicates within a host.
- Information about mutations that occur in different genome sequences of the monkeypox virus across different regions can thus provide important insights into how the virus evolves, its genetic diversity, and other factors that may be relevant to the development of diagnostic tools.
- The monkeypox virus, like other poxviruses, was thought to have a low rate of accumulating genetic changes compared to viruses with an RNA genome, such as SARS-CoV-2, which have a much higher rate of mutations.
- This rate is estimated to be as low as a couple of genetic changes per year for poxviruses. However, a recent study found that the observed rate of genetic changes in the virus was higher than expected, with an average of around 50 genetic changes.
- The faster-than-expected rate of evolution, combined with the rapid rise in monkeypox cases around the world, could be attributed to highly parallel evolution in a large number of individuals at the same time, as the current outbreak resulted from a superspreader event.
The APOBEC3 protein
- The study also suggests that several mutations found in new monkeypox virus sequences may have resulted from interaction between the virus genome and the Apolipoprotein B Editing Complex, a family of proteins coded by the human genome (or APOBEC3).
- These proteins protect against certain viral infections by editing the virus’s genome sequence as it replicates in the cell.
- As a result, some researchers believe that many of the genetic mutations in the monkeypox genomes from the current outbreak are relics of the effect of APOBEC3 and may not provide the virus with a significant evolutionary advantage.
- The monkeypox virus can infect a variety of hosts, including nonhuman primates and rodents, which could serve as natural reservoirs.
- Infections in the reservoir could also allow for continued transmission and mutation accumulation before spreading to cause human infections.
- Other studies have also suggested that the virus is still evolving, including deletions involving genes as seen in a few genomes from the current outbreak, which could point to newer ways in which the virus evolves with continued human-to-human transmission.
Lineages of monkeypox
- A lineage or clade is a group of genomes that have common and shared mutations as well as a common origin.
- The Central African (Congo Basin) clade and the West African clade of monkeypox virus were defined in the early 2000s in Africa, where several cases of the disease have been seen—the Congo Basin clade has been shown to be more transmissible and cause more severe disease.
- Researchers recently proposed a new system of naming monkeypox lineages because using the country or geography of origin could be discriminatory and possibly not in the right spirit.
- The Congo Basin clade is designated as clade 1 in the new proposed system, while the West African clade is divided into clades 2 and 3.
- This new system will also describe virus sub-lineages, with the original parent lineage denoted as ‘A,’ and its descendants as ‘A.1,’ ‘A.1.1,’ ‘A.2,’ and ‘B.1.’ Lineage B.1, which is a descendant of the A.1.1 lineage, denoted the current 2022 outbreak of monkeypox virus infections.
- Insights from the 2022 monkeypox outbreak The identification of this distinct lineage during the 2022 monkeypox outbreak suggests that a previously undetected and cryptic transmission of the virus has been occurring in multiple countries since at least around 2021, and was likely discovered due to increased awareness of the disease and the availability of diagnostic tools.
- By using a molecular approach for contact tracing and understanding virus transmission around the world, genomic surveillance of pathogens provides intriguing insights.
- As monkeypox cases continue to rise, it is critical to strengthen genomic surveillance for the monkeypox virus. Because data from the current outbreak suggest sustained human-to-human transmission, continuous genomic surveillance is critical for understanding the virus’s evolution and adaptation, in addition to providing useful data to epidemiologists.
- With COVID-19 on the rise and monkeypox on the horizon, the time has never been better, and the need has never been greater, to establish a sustainable system for genomic surveillance in India.
- The process of deciphering the exact order of base pairs in an individual is known as genome sequencing. What sequencing is all about is “deciphering” or reading the genome.
- The cost of sequencing varies depending on the methods used to read the genome or the accuracy required in decoding the genome.
Need for genome sequencing:
- Since the human genome was first sequenced in 2003, it has provided a new perspective on the relationship between disease and each individual’s unique genetic make-up.
- It is now known that nearly 10,000 diseases, including cystic fibrosis and thalassemia, are caused by a single gene malfunction.
- While genes may make some people resistant to certain drugs, genome sequencing has shown that cancer, too, can be understood through genetics rather than being viewed as a disease of specific organs.
India’s Genome Sequencing Efforts:
- The Centre for Scientific and Industrial Research (CSIR) sequenced the entire genome of a novel coronavirus.
- IndiGen Genome Project:
- In April 2019, the CSIR launched the IndiGen initiative, which was carried out by the CSIR-Institute of Genomics and Integrative Biology (IGIB) in Delhi and the CSIR-Centre for Cellular and Molecular Biology (CCMB) in Hyderabad.
- Using population genome data, the goal is to enable genetic epidemiology and develop public health technology applications.
- This has allowed us to benchmark the scalability of genome sequencing and computational analysis at the population scale within a specific time frame.
- The ability to decode humans’ genetic blueprint via whole genome sequencing will be a major driving force in biomedical science.
- The IndiGen programme aims to sequence the entire genomes of thousands of Indians from various ethnic groups.
- Genome India:
- The Indian government recently approved a gene-mapping project called “Genome India.”
- To construct a grid of the Indian “reference genome” in order to fully understand the types and nature of diseases and traits found in the diverse Indian population.
- The Centre for Brain Research at Bengaluru’s Indian Institute of Science serves as the nodal point for approximately 20 institutions.
India’s Genome Sequencing Challenges
- Very high goal: The goal was to sequence at least 5% of the samples, the bare minimum required to keep track of virus variants. This has so far been around 1%, owing to a lack of reagents and tools required to scale up the process.
- Limited Capacity: The ten laboratories can sequence about 30,000 samples per month, or 1,000 per day, which is six times less than what is required to meet the target.
- Funding crunch: Funding is repeatedly delayed. INSACOG requested Rs 100 crore, but funding did not arrive until March, when it received Rs 70 crore.
- Sample Collection: The healthcare system is already overburdened, and this is another task for them to sort and package samples and RNA preparations on a regular basis for shipping in a cold chain to sequencing centres, as well as record extensive metadata to make sequence information useful.
- Import Dependence: The Atma Nirbhar scheme, which prohibited imports of goods worth less than Rs 200 crore in order to promote local procurement, slowed the process of genome sequencing. Even after the exemption, some special plastics inadvertently remained subject to the import ban, causing problems with the process.
- International aspect: India’s image abroad suffers as a result of slow progress in genome sequencing, as all countries are required to upload data to a common global repository known as the ‘Global Initiative on Sharing All Influenza Data,’ or GISAID.
- Given the benefits of genome sequencing, it will aid in a better understanding of the human body and processes, as well as in the treatment of previously incurable diseases.
- Although there are some issues and challenges, they are manageable and can be resolved.